Sunlight is by far the most important environmental insult to the skin. Determination of the molecular basis of several inheritable photosensitivity syndromes, including Xeroderma pigmentosum and Rothmund-Thomson syndrome, has enhanced our understanding of the mechanisms of sun damage. The goal of this research proposal is the identification of genes whose mutations cause two of the remaining unelucidated heritable photosensitivity disorders-Kindler syndrome and actinic pruigo. DNA is available from a unique cohort of Kindler syndrome patients from Bocas del Toro, Panama and from several cohorts of AP patients from Saskatchewan, Keewatin in the Northwest territories and Norway House, Manitoba. Genotyping will be expedited by the availability of automated genome-wide scanning, which will be done on pooled DNA samples. Results will also be confirmed by manually analyzing the genotypes of individual samples. The candidate regions will be narrowed by genotyping at polymorphic sites. Mutations in DNA from affected individuals in the initial studies will be compared with different kindreds with these diseases.